Like pain relievers, vesicles in neurons come in slow-release and fast-release varieties. Hammarlund et al. reveal that the two varieties differ in how they attach to the cell membrane.

One reason that impulses can zip through the nervous system is that vesicles filled with neurotransmitters are attached to the membrane, ready to spill their contents into the synapse when a neuron is stimulated. But neurons also release peptides that can increase or reduce the sensitivity of nerve cells. These peptides reside in so-called dense core vesicles, which require multiple, rapid stimuli before they disgorge their contents. Dense core vesicles might be slower because they aren't hitched to the membrane and have to travel there after stimulation. But at least some of these vesicles are docked, researchers have found, so another possibility is that dense core vesicles and neurotransmitter vesicles are attached to the membrane in different ways.

Hammarlund et al. tested this hypothesis by comparing the two vesicle types in C. elegans neurons. The scientists determined that neurotransmitter-filled vesicles cluster at the synapse, whereas dense core vesicles disperse around the axon. Dense core vesicles remain aloof from the membrane if the protein CAPS is lacking, the team found. However, CAPS isn't necessary for neurotransmitter vesicles to dock. Instead, these vesicles need a related protein called UNC-13.

Previous work suggests that UNC-13 promotes docking by interacting with a membrane protein called syntaxin. Syntaxin can double over on itself, and UNC-13 probably pries open syntaxin to allow attachment. The results from Hammarlund et al. suggest that CAPS also opens up syntaxin. Their findings also suggest that CAPS and UNC-13 might help docked vesicles fuse with the membrane after stimulation.

Dense core vesicles and neurotransmitter vesicles thus appear rely on unique mechanisms to hook onto the membrane. Nailing down how these differences translate into changes in release speed will require further research.